Treatment of Interstitial Lung Disease (ILD) Flare
For an acute ILD flare, glucocorticoids serve as short-term bridge therapy while avoiding long-term use (>3-6 months), with treatment selection depending critically on whether this represents a standard flare versus rapidly progressive disease and the underlying systemic autoimmune rheumatic disease (SARD) subtype. 1
Distinguishing Flare Type and Initial Management
Standard ILD Flare (Non-Rapidly Progressive)
Short-term glucocorticoids are appropriate as bridge therapy while escalating definitive immunosuppressive treatment. 1
- Glucocorticoids may be used temporarily for acute flares or as a bridge to more definitive therapy changes 1
- Avoid long-term glucocorticoid therapy (>3-6 months) for progressive ILD 1
- For SSc-ILD specifically, there is a strong recommendation against glucocorticoids due to moderate-certainty evidence of scleroderma renal crisis risk 1
- For other SARD-ILD subtypes, short-term glucocorticoids are conditionally recommended 1
Rapidly Progressive ILD (RP-ILD)
For RP-ILD, pulse intravenous methylprednisolone is conditionally recommended as first-line treatment, combined with aggressive immunosuppression. 1
- Upfront combination therapy is recommended over monotherapy for RP-ILD 1
- Triple therapy (glucocorticoids + calcineurin inhibitor + cyclophosphamide) for confirmed or suspected MDA-5 positive disease 1, 2
- Double or triple therapy for RP-ILD without confirmed MDA-5 1
- First-line RP-ILD options include: rituximab, cyclophosphamide, IVIG, mycophenolate, calcineurin inhibitors (CNI), and JAK inhibitors 1
Disease-Specific Treatment Escalation for Standard Flares
If Already on First-Line Therapy with Progression
Switch to or add mycophenolate, rituximab, cyclophosphamide, or nintedanib as second-line options for most SARD-ILD. 1
For Systemic Sclerosis (SSc-ILD):
- Mycophenolate is preferred if switching from first-line therapy 1
- Rituximab can be added to mycophenolate or used as monotherapy 1
- Tocilizumab is conditionally recommended 1
- Nintedanib may be added, particularly with progressive fibrosing disease on HRCT 1
- Strongly recommend against long-term glucocorticoids 1
For Inflammatory Myopathy (IIM-ILD):
- Calcineurin inhibitors (tacrolimus 0.075 mg/kg/day targeting trough 5-10 ng/mL) 1
- JAK inhibitors 1
- IVIG may be added 1
- Conditionally recommend against tocilizumab 1
For Rheumatoid Arthritis (RA-ILD):
- Adding pirfenidone is conditionally recommended, particularly with UIP pattern 1
- Tocilizumab is an option 1
For Mixed Connective Tissue Disease (MCTD-ILD):
For Sjögren's Disease (SjD-ILD):
- Mycophenolate, rituximab, cyclophosphamide, or nintedanib 1
- Conditionally recommend against tocilizumab 1
Monitoring During Treatment Escalation
Mycophenolate Monitoring:
Rituximab Monitoring:
- Hepatitis B, hepatitis C, and latent TB screening before initiation 1
- CBC with differential at 2-4 month intervals 1
- Dosing: 1g IV every 2 weeks for 2 doses, repeated every 24 weeks as needed 1
Tacrolimus Monitoring:
- Trough levels, comprehensive metabolic panel, magnesium, phosphorus monitored 1-2 times weekly for first month, monthly for 3 months, then every 2-3 months 1
- Blood pressure monitoring 1
Critical Pitfalls to Avoid
- Do not rely on long-term glucocorticoids (>3-6 months) for progressive ILD management 1
- Prompt corticosteroid therapy in acute flares may improve survival; delays worsen outcomes 4
- Patients with CT fibrosis have lower response to steroids and higher mortality 4
- In mechanically ventilated patients, avoid high PEEP settings that cause overdistension, as this is associated with mortality in fibrotic ILD 4
- Early referral to lung transplant centers is essential given high mortality rates without transplantation 5, 6
- For RP-ILD, early referral for lung transplantation is recommended over later referral after progression 1